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New tool for screening ovarian cancer in focus
Clinicians face challenges when it comes to detecting ovarian cancer: 70% of women with ovarian cancer are diagnosed with advanced disease.1 New research indicates that a potential screening strategy developed for post-menopausal women at average risk might be of benefit.2 The data was released prior to the Alexandria, VA-based American Society of Clinical Oncology's June 2010 annual clinical conference.
Scientists are now focusing on CA-125, the protein which has been used for many years to predict ovarian cancer recurrence. The strategy being researched uses a mathematical model that combines trends in CA-125 blood test results and a patient's age, followed by transvaginal ultrasound and referral to a gynecologic oncologist, if necessary. Data indicates this approach is feasible and produces few false-positive results.2
There has been a lot of excitement generated over new markers and technologies in ovarian cancer over the last 10 years, according to Karen Lu, MD, professor in The University of Texas MD Anderson Cancer Center's Department of Gynecologic Oncology in Houston,.
"I and other scientists in the gynecologic oncology community thought we would ultimately find a better marker than CA-125 for the early detection of the disease," says Lu, the current trial's principal investigator. "After looking at new markers and testing them head-to-head in strong, scientific studies, we found no marker better than CA-125."
Algorithm is key tool
A CA-125 blood test serves as a good indicator of an ovarian tumor's response to treatment after surgery or during chemotherapy. However, when it has been eyed for early disease detection, the marker can become elevated for reasons other than ovarian cancer, which leads to false positives.
Steven Skates, PhD, associate professor in the Department of Medicine at Harvard Medical School and associate in Biostatistics (Medicine) at the Cancer Center at Massachusetts General Hospital, both in Boston, developed the algorithm used in research for predicting the risk of ovarian cancer. The algorithm, known as Risk of Ovarian Cancer Algorithm (ROCA), is a mathematical model based on the patient's age and CA-125 score.3 In addition to serving as investigator on the U.S. trial, Skates and research partners are using the ROCA algorithm in a large-scale trial in the United Kingdom. The results from the overseas trial, which includes over 200,000 women, should be known by 2015.
Look at the research
For the prospective, single-arm U.S. study, 3,252 women were enrolled from seven sites across the country. All were healthy, post-menopausal women, ages 50-74, with no strong family history of breast or ovarian cancer. The study's primary endpoint was specificity; in addition, the study looked at the positive predictive value (the number of operations required to detect a case of ovarian cancer).
Scientists administered a baseline CA-125 blood-test to each woman. Using the ROCA tool, women were assigned to one of three risks groups, with the respective follow-up. Women in the "low" group returned in a year for a follow-up blood test, with those in the "intermediate" group receiving further monitoring with repeat CA-125 blood test in three months. Women assigned to the "high" category were referred to receive transvaginal sonography (TVS) and to see a gynecologic oncologist.
Based on the women's CA-125 change over time, the average annual rate of referral to the intermediate and high groups were 6.8% and .9%, respectively. Cumulatively, 85 women (2.6%) were determined to be high risk, and thereby received the TVS and were referred to a gynecologic oncologist. Of those women, eight underwent surgery: five were found to have ovarian cancer, three with invasive and two with borderline disease; three had benign tumors, for a positive predictive value of 37.5%. The screening failed to detect two borderline ovarian cancers.
The three invasive ovarian cancers detected in the study were high-grade epithelial tumors, the most aggressive form of the disease, and were caught in their early stages, when the disease is not only treatable, but most often curable. The study findings provide early evidence that ROCA followed by TVS is a feasible strategy for screening women over 50 years old, researchers conclude.2
While encouraging, the findings are neither definitive, nor immediately practice-changing, the U.S. researchers emphasize. CA-125 is shed by only 80% of ovarian cancers, says Robert Bast, MD, vice president for translational research at MD Anderson and a co-investigator on the U.S. study.
"At present, we are planning a second trial that will evaluate a panel with four blood tests including CA-125 to detect the cancers we may otherwise miss with CA-125 alone," says Bast. "The current strategy is not perfect, but it appears to be a promising first step."